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Kidney Disease Research Updates
Winter 2013

KUH Conferences Advance Understanding, Approaches to Fields

From NIDDK Director’s Update

In February, NIDDK’s Division of Kidney, Urologic, and Hematologic Diseases held the “NIDDK KUH Winter Conferences 2012,” a series of workshops on topics including kidney genetics, hematopoiesis, kidney morphology, and nonmalignant hematology. The workshops served many goals.

On Feb. 11 and 12, the first conference of the group, “Whole Genome Approaches to Complex Kidney Diseases,” met in Bethesda, MD, to address questions such as how to help the nephrology research community make use of next-generation sequencing capabilities that have made whole exome studies—studies that use an approach that decodes the 1 to 2 percent of the genome that contains protein-coding genes—accessible for clinical research.

The conference convened to evaluate study designs and existing DNA repositories and databases that are relevant to whole exome studies; to learn about emerging statistical approaches to effectively evaluate and analyze the myriad variants identified in whole exome studies; to consider the optimal ways to perform whole exome research, in terms of ethical, legal, and social aspects; and to discuss how best to transmit complicated findings to patients when these whole exome approaches become a routine part of clinical nephrology practice.

“Whole exome testing is already being marketed to consumers and will likely be a part of routine clinical practice, at least when addressing particular clinical problems, within the next decade,” said NIDDK intramural researcher Dr. Jeffrey Kopp, co-chair of the conference. “This will require physicians who see kidney patients to help their patients understand such concepts as carrier status, recessive genes, susceptibility alleles, and clinical risk estimates. Physicians will often require additional training in genetic medicine and access to NIH databases that provide current information on the clinical implications of particular genetic variants.”

On Feb. 13 and 14, NIDDK held a conference, “Quantitative Morphology in Kidney Research,” to review techniques to count the number of glomeruli and some of their component cells, called podocytes, in kidneys. There is evidence that glomerular endowment is affected by genetic factors and by environmental exposures during gestation, and that low glomerular numbers are associated with an increased risk for chronic kidney disease in adulthood. Speakers discussed stereology, a set of techniques used to estimate features of three-dimensional objects from lower-dimensional samples, and considered stereologically valid approaches to assessing kidney samples from humans and experimental animals.

“Stereology offers a sophisticated suite of methods to count and measure objects,” said Kopp. “These methods can be applied to research material ranging from whole organs to a few tissue sections. It is critical that researchers select the most appropriate method for their purpose and their material, as only stereologically sound techniques will produce valid data and lead to sound conclusions.”

On Feb. 20, the NIDDK held a “state of the science” workshop, “Regulatory Determinants of Hematopoietic Stem Cell Self-Renewal, Lineage
Commitment and Terminal Differentiation: New Insights.” The workshop’s objectives were to provide an opportunity for research leaders in the field of hematopoietic stem cell (HSC) biology to examine current understanding of how HSC self-renewal, lineage commitment, and terminal differentiation are regulated; to define knowledge gaps and key unanswered questions in these critical aspects of HSC biology; and to define opportunities, directions, and priorities for future research to address these questions.

NIDDK Senior Scientific Advisor and Program Director for Hematology Research Dr. Daniel Wright, principal organizer of the workshop, was pleased with the capacity attendance of more than 140 researchers from around the country and Canada, reflecting a high level of interest in the workshop’s focus and objectives.

On Feb. 23 and 24, NIDDK’s Nonmalignant Hematology Research Network, or HEME-NET, held a meeting in Rockville, MD. The workshop marked the first time this group of NIDDK hematology grantees had met face-to-face to share research activities, build relationships between researchers in the field of NIDDK hematology interests, learn about NIDDK-funded resources available through the Centers of Excellence in Molecular Hematology, and assemble a prototype for the network.

“The meeting was enthusiastically attended by investigators, who overwhelmingly supported the notion of building a network to facilitate communication and collaboration among members and to inform the community at large about research accomplishments in nonmalignant hematology,” said NIDDK Hematology Program Director Dr. Terry Bishop. “Attendees felt that HEME-NET could leverage and strengthen the field by fostering the exchange of ideas and by posting collaborative opportunities and available resources.”

NIDDK workshops continued through the spring. In April, experts convened to discuss “Glomerular Disease: Pathophysiology, Biomarkers, and Registries for Facilitating Translational Research.” Goals addressing glomerular disease included discussing mechanisms that initiate and drive progression of glomerular diseases to end-stage kidney disease; exploring targets and pathways to therapeutic development; assessing existing biomarkers that define diagnosis, initiation, progression, and relapse; and discussing approaches to potential cooperation with industry, academia, government, and others. International experts from industry and academia as well as representatives from the NIH, FDA, and private foundations discussed the challenges and pitfalls of glomerular disease research and formulated the path forward.